Sophisticated RNA
by MikeGeneThe non-teleological perspective views RNA as a primitive, ancient relic of the process of abiogenesis. The teleological perspective views RNA as a sophisticated molecule that plays an essential control function within the cell and has never existed apart from its cellular context.
While RNA is crucial to all living things, I think eukaryotes have more fully exploited its ability to control the proteome (a cell's protein complement). A simple fact from cell biology explains this. In prokaryotes, the process of RNA synthesis (transcription) is coupled to the process of protein synthesis (translation). This allows bacteria to more efficiently express their genes and the bacterial cell design is all about efficiency. But eukaryotes trade efficiency for flexibility, and as such, have a nucleus where the genome is physically separated from the ribosomes. This means there is a much larger window of opportunity to process and modify protein-encoding RNA in eukaryotes, which in turn means the greater potential for control. One such control mechanism exploited by eukaryotes is alternative-splicing, where a single gene can give rise to dozens of gene products that are variations on a theme.
In his book, Muscles as Molecular and Metabolic Machines, Peter Hochacka wrote:
It is accepted that many (indeed most) of the components required for integrated muscle function are proteins, which usually can be expressed in more than one form (so-called isoforms, isoproteins, or isoenzymes). Isoforms of the components of muscle tissue are formed in a variety of ways: at the genetic level, with different genes specifying the different forms and timing of their expression; at the translation level, with different splicing patterns generating different isoforms; or at the post-translational level, with the modification of the gene polypeptide products generating different isoforms of those products. This means that, in principle, muscle cells could be put together in many different ways "“ in as many ways as there are combinations of the isoprotein components that together make up the tissue we call muscle.
A question that will arise over and over again in our analysis, therefore, will be whether or not all possible combinations are or ever can be realized. The answer to that question will invariably be negative. Indeed it will be argued that, in some of the most finely tuned and well adapted muscles, a single unique combination from the myriad of statistically possible combinations seems to be selected at the expense of all others.
Or as he explains later:
We suggest that the isoform design of the overall system is one reason why the realized number of muscle types is only a minute fraction of the maximum number theoretically possible. Just as the drive shaft of a sports car would not do in a cement truck, troponin c isoforms in fast muscles many not be suitable for slow muscles; fast muscle Ca ATPase may be debilitating to slow muscles, while slow muscle presynaptic Ca channels would simply not work well enough in fast muscle, and so forth.
While we can credit RNA and alternative splicing for generating most of these isoforms, what controls whether and where the RNA is spliced?
According to a recent study, RNA is again involved:
As reported in the January 1 issue of G&D, a UCLA research team led by Dr. Douglas Black has shown how microRNAs regulate alternative splicing during muscle development. The researchers determined that the muscle-specific microRNA miR-133 targets the alternative splicing factor, nPTB, during early myogenesis. The resulting decrease in nPTB protein levels alters the splicing of muscle-specific mRNAs in such a way as to promote muscle cell differentiation. The targeting of this splicing factor allows the microRNA to control a larger temporal program of muscle cell gene expression through not just the direct translational regulation of mRNAs, but also by altering the splicing of important mRNAs.
From the non-teleological perspective, RNA appeared before cellular physiology and genome-proteome interactions ever existed and was selected for the simple, myopic reason of self-replication. It's quite a stroke of luck that the same molecule whose properties were shaped in this primitive setting have been able to play such an important role in the evolution of something as sophisticated as muscle tissue, helping cells reach "a single unique combination from the myriad of statistically possible combinations."
Another perspective would allow us to view RNA as something that was deeply embedded within cells to faciliate their evolution.
January 4th, 2007 at 2:19 pm
Hi Mike,
Nice post. While I appreciate the significance of elucidating the telic vs. non-telic perspectives on RNA function, do you believe there is a testable to way to distinguish between the two competing hypotheses?
Though you do make an interesting point in the post re: RNA not existing outside of a cellular context. Indeed the problems with abiotic RNA synthesis are significant. Even under ideal circumstances… RNA synthesis is difficult. Most of the major companies marketing RNA oligos won't let you order anything more than 70 bases or so… and when you do that… you'll generally be on the line with their technical staff.
I do believe most of the difficulties associated with RNA synthesis present a significant… an enormous barrier to origin of life theories, but such negative evidence can't stand in support of the telic perspective.
Again, the differing points of view are noteworthy, but how does one test, in this case, the telic vs. non-telic perspective?
Comment by kallikak — January 4, 2007 @ 2:19 pm
January 4th, 2007 at 3:08 pm
Kallikak makes a good point.
Experimenters with differing opinions on the issue of teleology can and should be able to do the same work.
These results can be obtained regardless of the metaphysic involved and regardless of whether they lend support to one view or the other.
This is, in my humble opinion, what biology should be about. Like a chemist investigating reactions and analysing chemicals, the experimental biologist should be doing the same.
This isn't to say he can't have an opinion about the evolutionary history of biological elements, but that really should be viewed apart from what can be studied and known. It is a secondary question, if that, to the empirical, experimental and observational science.
As Kallikak asks:
If one can't test for the perspective, and if the perspective then is irrelevant to the work then why worry about the perspective?
Leave telic/non-telic perspectives for the blogs and quit attaching them to the empirical science.
Publish results whether they come attached with evolutionary references or not and whether they support the paradigm or not.
If one irrelevant perspective is allowed then allow either.
If one historic speculation is worthy of dissemination then so is the other.
(sorry for having nothing to contribute on the exact issue of recombination and splicing.)
Comment by Pez — January 4, 2007 @ 3:08 pm
January 4th, 2007 at 3:49 pm
Mike, this may be OT, but I found a paper during an unrelated search under Quantitative Biology and wondered if you are familiar with it or the author. I was looking for a story I saw somewhere (where!?) last week about the development of a new computer program that has a database of all possible DNA sequences, which is planned to be used to identify all the sequences we NEVER see in genomes of any microbe, plant or animal. The "forbidden sequences," which I thought was an interesting approach.
This paper's is Unified theory of express evolution, directed biology, and guiding genome by Mark Ya. Azbel', a physicist at Tel Aviv University. It looks like Azbel' has written quite a few papers attempting to quantify the appearance and conservation of mortality in life forms - that which enables evolution - and links this to Major Mass Extinction [MME] events during the history of life that appear to account for "Punctuated Equilibrium" - rapid adaptive evolution - observed in the fossil record.
Here is a related paper of Azbel's in HTML format.
It just occurs to me that your telic view of RNA as an essential control function in the cell might be related to the conserved RNA coding in the "junk" as part of something like this 'guiding genome'. I'm not qualified to parse it, but it's intriguing anyway. So I'll just repeat a Mattick quote [Scientific American article] from your idthink link -
"…Eventually, if the volume of troublesome information becomes unsustainable, the orthodoxy must collapse. We may be witnessing such a turning point in our understanding of genetic information."
Comment by Joy — January 4, 2007 @ 3:49 pm
January 4th, 2007 at 3:57 pm
Hi kallikak,
Yes, the long-term goal would be to reach a point where meaningful, testable hypotheses can be developed to distinguish between the two views. In my opinion, the best way to reach that goal is to flesh out a telic perspective that is able to stand on its own. As many around here know, I am inspired by Jacob's observation: Scientific advances often come from uncovering a hitherto unseen aspect of things as a result, not so much of using new instruments, but rather of looking at objects from a different angle. The telic perspective just allowed me to connect, for example, something from Hochachka's book (which I read years ago) and a new study that just came out, deepening thoughts about the general purpose of RNA.
As more and more look from this different angle, and seriously begin to think it through, I expect testable hypotheses to eventually surface (if for no other reason that there are many who are smarter and more knowledgeable than me). But it would first help if teleologists focused on providing a model that tests not against a non-telic view, but against empirical reality itself. If this model can begin to develop a positive track record, sooner or later it will come into direct conflict with the non-telic view. Yet when it does, we won't necessarily be making predictions to falsify the non-telic view; we'll be making predictions that are superior to the non-telic view.
Right now, the non-telic view enjoys a monopoly on the mind because most teleologists focus on either battling evolution or finding ways to make peace with empirical research. Thus, as I hint in my essay, the non-telic view is just that "“ only one way to view reality and it has no way of distinguishing itself from the view I have begun the lay out. The non-telic view has many believing that the ancient earth was an "˜RNA World' that transitioned to cellular life as we know it. But the RNA World itself is just a view, a way of looking at things uncovered by cell and molecular biology. Without a competing telic view, it is not surprising the RNA world entices so many. If anything, the emergence of a telic view allows everyone to see the non-telic view is assumption-dependent and not an output of the data.
So again, I take a long-term approach. After all, I'm a front-loader.
[BTW, I appreciate the comments about RNA itself. It is interesting that a macromolecule so well-suited for cellular evolution is so ill-suited for life outside the cell.]
Comment by MikeGene — January 4, 2007 @ 3:57 pm
January 4th, 2007 at 8:28 pm
Joy,
In case you haven't found it yet, there's information about that database of "forbidden" DNA elements here.
Comment by Mesk — January 4, 2007 @ 8:28 pm
January 4th, 2007 at 8:35 pm
Thanks, Mesk! I went through the ScienceDaily archives, then thought maybe it was a link from one of the ScienceBlogs, then ended up on the NL preprint server (after PNAS and PLoS). Was beginning to wonder if I dreamed it! §;o)
Comment by Joy — January 4, 2007 @ 8:35 pm